Four A6-TCR/peptide/HLA-A2 structures that generate very different T cell signals are nearly identical

Immunity. 1999 Jul;11(1):45-56. doi: 10.1016/s1074-7613(00)80080-1.

Abstract

The interactions of three singly substituted peptide variants of the HTLV-1 Tax peptide bound to HLA-A2 with the A6 T cell receptor have been studied using T cell assays, kinetic and thermodynamic measurements, and X-ray crystallography. The three peptide/MHC ligands include weak agonists and antagonists with different affinities for TCR. The three-dimensional structures of the three A6-TCR/peptide/HLA-A2 complexes are remarkably similar to each other and to the wild-type agonist complex, with minor adjustments at the interface to accommodate the peptide substitutions (P6A, V7R, and Y8A). The lack of correlation between structural changes and the type of T cell signals induced provides direct evidence that different signals are not generated by different ligand-induced conformational changes in the alphabeta TCR.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Substitution / immunology
  • Gene Products, tax / biosynthesis
  • Gene Products, tax / chemistry
  • Gene Products, tax / immunology
  • HLA-A2 Antigen / biosynthesis
  • HLA-A2 Antigen / chemistry*
  • HLA-A2 Antigen / physiology
  • Humans
  • Kinetics
  • Macromolecular Substances
  • Major Histocompatibility Complex / physiology
  • Peptides / agonists
  • Peptides / antagonists & inhibitors
  • Peptides / chemistry*
  • Peptides / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / agonists
  • Receptors, Antigen, T-Cell, alpha-beta / antagonists & inhibitors
  • Receptors, Antigen, T-Cell, alpha-beta / chemistry*
  • Receptors, Antigen, T-Cell, alpha-beta / physiology
  • Signal Transduction / immunology*
  • Surface Properties
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Thermodynamics

Substances

  • Gene Products, tax
  • HLA-A2 Antigen
  • Macromolecular Substances
  • Peptides
  • Receptors, Antigen, T-Cell, alpha-beta